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Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer.

ABSTRACT: Numerous genetic studies have been conducted regarding the occurrence of colorectal cancer (CRC) and the prognosis using microarrays. However, adequate investigations into the diagnostic application of microarrays have yet to be performed. The simplicity and accuracy of diagnosis and prognosis tracking are important requirements for its processes, and the use of blood cells for diagnosis is considered to be suitable to meet these requirements. The patients involved in the study were 28 preoperative patients with CRC and 6 healthy individuals who served as controls. RNA was extracted from the blood cells of the patients and analyzed using a sense/antisense RNA custom microarray. In the patients with CRC, the expression levels of 20 sense RNA and 20 antisense RNA species were identified as being significantly altered compared with that of the healthy volunteers (P<0.05; fold-change, >2.0). Cluster analysis of these RNA species revealed that the top 10 antisense RNAs significantly clustered patients with cancer and healthy individuals separately. Patients with stage I or II CRC exhibited significant changes in the expression levels of 33 sense and 39 antisense RNA species, as compared with healthy volunteers (P<0.01; fold-change >2.0). Cluster analysis demonstrated that patients with stage I or II CRC and healthy volunteers formed separate clusters only among the top 20 antisense RNA species. A tracking study of expression levels of haloacid dehalogenase-like hydrolase domain-containing 1 (HDHD1) antisense RNA was performed and a significant difference was identified between the CRC and healthy groups revealing that the levels at one week and three months following surgical removal of the cancerous tissue, decreased to almost same levels of the healthy individuals. The results of the current study indicate that HDHD1 antisense RNA may serve as a potential biomarker for the prognosis of CRC.

SUBMITTER: Kurokawa T

PROVIDER: S-EPMC5587960 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer.

Kurokawa Tomohiro T Kohno Keisuke K Nagai Kentaro K Chiba Mitsuru M Pak Sugiru S Murata Soichiro S Fukunaga Kiyoshi K Yasue Hiroshi H Ohkohchi Nobuhiro N

Oncology letters 20170715 3

Numerous genetic studies have been conducted regarding the occurrence of colorectal cancer (CRC) and the prognosis using microarrays. However, adequate investigations into the diagnostic application of microarrays have yet to be performed. The simplicity and accuracy of diagnosis and prognosis tracking are important requirements for its processes, and the use of blood cells for diagnosis is considered to be suitable to meet these requirements. The patients involved in the study were 28 preoperat ...[more]

PMID: 28927104

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Project description:Background and objectivesColorectal cancer remains an important public health problem in the context of the COVID-19 (Corona virus disease 2019) pandemic. The decline in detection rates and delayed diagnosis of the disease necessitate the exploration of novel approaches to identify individuals with a heightened risk of developing colorectal cancer. The study aids clinicians in the rational allocation and utilization of healthcare resources, thereby benefiting patients, physicians, and the healthcare system.MethodsThe present study retrospectively analyzed the clinical data of colorectal cancer cases diagnosed at the Affiliated Hospital of Guilin Medical University from September 2022 to September 2023, along with a control group. The study employed univariate and multivariate logistic regression as well as LASSO (Least absolute shrinkage and selection operator) regression to screen for predictors of colorectal cancer risk. The optimal predictors were selected based on the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. These predictors were then utilized in constructing a Nomogram Model for predicting colorectal cancer risk. The accuracy of the risk prediction Nomogram Model was assessed through calibration curves, ROC curves, and decision curve analysis (DCA) curves.ResultsClinical data of 719 patients (302 in the case group and 417 in the control group) were included in this study. Based on univariate logistic regression analysis, there is a correlation between Body Mass Index (BMI), red blood cell count (RBC), anemia, Mean Corpuscular Volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), Red Cell Distribution Width-Standard Deviation (RDW-SD), and the incidence of colorectal cancer. Based on the findings of multivariate logistic regression analysis, the variables of BMI and RBC exhibit a decrease, while anemia and PLT demonstrate an increase, all of which are identified as risk factors for the occurrence of colorectal cancer. LASSO regression selected BMI, RBC, anemia, and PLT as prediction factors. LASSO regression and multivariate logistic regression analysis yielded the same results. A nomogram was constructed based on the 4 prediction factors identified by LASSO regression analysis to predict the risk of colorectal cancer. The AUC of the nomogram was 0.751 (95% CI, OR: 0.708-0.793). The calibration curves in the validation and training sets showed good performance, indicating that the constructed nomogram model has good predictive ability. Additionally, the DCA demonstrated that the nomogram model has diagnostic accuracy.ConclusionThe Nomogram Model offers precise prognostications regarding the likelihood of Colorectal Cancer in patients, thereby helping healthcare professionals in their decision-making processes and promoting the rational categorization of patients as well as the allocation of medical resources.

Project description:BackgroundCis-natural antisense transcripts (cis-NATs) are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs), which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs.ResultsWe applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq) to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa). Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set), 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks.ConclusionsOur study profiles an abundance of cis-NATs and nat-siRNAs in rice. These data are valuable for gaining insight into the complex function of the rice transcriptome.

Project description:AimThe study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy.MethodsThe study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.ResultsData analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04).ConclusionAberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

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Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer.

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Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer.

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